This proposal describes a plan for a Preventive Oncology Academic Award and my personal development towards a multi-disciplinary approach to cancer epidemiology. Two project are described, the first one analyzes the extent to which heredity contributes to lung cancer etiology in two different ethnic groups, African Americans and Mexican Americans and in patients diagnosed before 45 years of age. This project is built upon an on-going study. During the award period, we will obtain detailed environmental and family history information from personal interviews. These data will be integrated with cyto- and molecular genetic markers. Using a family study design and segregation analysis (mixed and regressive models) as the primary statistical tool, we will determine: a) risk of cancer in relatives and patient's clinical and demographic characteristics associated with such increase; b) etiologic model(s) and parameter estimates; c) genetic heterogeneity to establish whether certain molecular, cytogenetic, clinical, and demographic parameters can discriminate between the hereditary and non-hereditary cases; d) identify specific kindreds for linkage analysis. These studies will enhance the knowledge of gene-environment interactions in lung carcinogenesis, identify groups of individuals and families who are at increased risk, and may help in identifying oncogenic mechanisms. In the second project we will analyze mutagen sensitivity in a cohort of 225 adult Hodgkin's disease patients enrolled since 1987 in a study of genotoxicity. During this award period, we will interview the patients to collect epidemiological data (risk factors, family history of cancer, reproductive history, second malignancies). Annual follow-up contacts will be done to update health histories. Epidemiologic and cytogenetic data will be integrated to analyze baseline, inter- and intra-individual differences in susceptibility to genetic damage. We will determine long-term genotoxicity of different treatments and the risk of adverse outcomes (second malignancies and reproductive events). The research projects outlined in this award will broaden my understanding of the interactions of cyto and molecular genetic markers and epidemiologic risk factors related to the etiology of lung cancer and in the understanding of genetic susceptibility induced by chemotherapeutic treatments.